Abstract
Recent studies associated rapid eye movement sleep behavior disorder (RBD) in Parkinson’s disease (PD) with severe cognitive impairment and brain atrophy. However, whole-brain functional connectivity has never been explored in this group of PD patients. In this study, whole-brain network-based statistics and graph-theoretical approaches were used to characterize resting-state interregional functional connectivity in PD with probable RBD (PD-pRBD) and its relationship with cognition. Our sample consisted of 30 healthy controls, 32 PD without probable RBD (PD-non pRBD), and 27 PD-pRBD. The PD-pRBD group showed reduced functional connectivity compared with controls mainly involving cingulate areas with temporal, frontal, insular, and thalamic regions (p < 0.001). Also, the PD-pRBD group showed reduced functional connectivity between right ventral posterior cingulate and left medial precuneus compared with PD-non pRBD (p < 0.05). We found increased normalized characteristic path length in PD-pRBD compared with PD-non pRBD. In the PD-pRBD group, mean connectivity strength from reduced connections correlated with visuoperceptual task and normalized characteristic path length correlated with processing speed and verbal memory tasks. This work demonstrates the existence of disrupted functional connectivity in PD-pRBD, together with abnormal network integrity, that supports its consideration as a severe PD subtype.
Highlights
Concerning resting-state functional MRI prior works in Parkinson’s disease (PD) with vPSG confirmed RBD diagnosis found decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex[14], decreased amplitude of low-frequency fluctuations in the primary motor and premotor cortices[15], as well as reduced posterior functional connectivity based on right superior occipital g yrus[16]
We hypothesize that PD patients with probable RBD will show a reduction in brain functional connectivity compared with healthy controls and PD patients without probable RBD and the reduction will be associated with cognitive impairment
Differences between healthy control and PD groups were observed for sex, subsequent analyses that included both groups were controlled by this variable
Summary
Concerning resting-state functional MRI (rs-fMRI) prior works in PD with vPSG confirmed RBD diagnosis found decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex[14], decreased amplitude of low-frequency fluctuations in the primary motor and premotor cortices[15], as well as reduced posterior functional connectivity based on right superior occipital g yrus[16]. A network-based perspective conceptualizes the brain as a complex network and allows characterizing dynamic interactions between regions through Network-Based Statistics (NBS) and graph-derived metrics[17] In this context, Li et al.[18], by graph-derived metrics, found extensive changes of nodal properties in PD-pRBD than PD-non pRBD in comparison with healthy controls in the neocortex and limbic system; as well as enhanced nodal efficiency in the bilateral thalamus and betweenness centrality in the left insula, and reduced betweenness centrality in the right dorsolateral superior frontal gyrus in PD-pRBD compared with PD-non pRBD. The development of the threshold-free network-based statistics (TFNBS) method[19], which, unlike NBS, does not require the a priori definition of a component-defining threshold and generates edge-wise significant values, has been proposed as a step forward This approach revealed in isolated RBD a disruption of posterior functional c onnectivity[20]. We hypothesize that PD patients with probable RBD will show a reduction in brain functional connectivity compared with healthy controls and PD patients without probable RBD and the reduction will be associated with cognitive impairment
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